1. Field of the Invention
The present invention relates to a method of manufacturing a microfluidic chip, a microfluidic chip, and an apparatus for generating surface plasmon resonant light.
2. Description of the Related Art
In the past, a molecular interaction detecting apparatus using surface plasmon resonance which is induced by radiating light a metal surface with light was known.
For example, Japanese Unexamined Patent Application, First Publication No. 2006-208069 discloses an apparatus in which a metal thin film is formed at a detecting portion of a flow channel which allows a solution including biological molecules to flow through, an antibody modified by a fluorescent molecule is fixed to the surface of the metal thin film, and changes in fluorescent signals from the fluorescent molecule can be detected when molecular interaction (bonding) occurs between the antibody and a detection subject.
In the apparatus described in Japanese Unexamined Patent Application, First Publication No. 2006-208069, generally, a prism is required in order to irradiate, with a laser light, the surface of the metal thin film at a specific incident angle.
There was a problem in that the size of the apparatus inevitably increases for the control of the laser radiation angle and the like.
In contrast to this, in the micro blade described in Japanese Unexamined Patent Application, First Publication No. 2008-286778 and a surface plasmon excitation-enhanced fluorescent microscope using the micro blade, the limitation in the laser radiation angle can be alleviated by forming a regular periodic structure (grating) on the metal surface of a detecting portion.
Therefore, it is disclosed that a decrease in the size of the apparatus and the simplification of an optical system can be achieved with no need for the prism.
A usual conventional method of forming the periodic structure is a method in which a resist mask having a periodic pattern that corresponds to the periodic structure is formed on a substrate made of SiO2 or the like, and the substrate is etched.
For example, there is a method in which a grating-like resist mask is formed by radiating, with a He—Cd laser, a positive-type resist using a double-beam interference method (“Optical microscopic observation of fluorescence enhanced by grating-coupled surface plasmon resonance” Keio Tawa, et al. OPTICS EXPRESS, 2008, Vol. 16, No. 13, 9781-9790).
In addition, a method in which a negative-type resist is coated on a flow channel formed on a SiO2 substrate, and the resist is worked into a grating using dual-photon absorptiometry in which a femtosecond laser is used (“Formation of subwavelength optical elements inside a microfluidic channel using femtosecond laser lithography” Norihiro Furukawa, Hiroaki Nishiyama, Yoshinori Hiratal 6th Symposium on “Microjoining and Assembly Technology in Electronics”, Feb. 2-3, 2010, Yokohama).
However, in any of the above methods, it is necessary to form a resist which has a shape corresponding to the periodic structure and has been subjected to an ultrafine working on the substrate.
That is, there is a problem in that the working accuracy of the periodic structure is dependent on the working accuracy of the resist.
The working accuracy of the resist is influenced by complicated factors such as the chemical composition of a resist composition, the adhesiveness between the substrate and the resist, etching characteristics after formation of the resist pattern, laser irradiation conditions, and the like.
In addition, there are frequent cases in which it is difficult to uniformly form a non-patterned resist in the fine structures of the microfluidic channel and the like on the substrate.
The invention has been made in consideration of the above circumstances, and an object of the invention is to provide a method of manufacturing a microfluidic chip in which a periodic pattern and a periodic structure can be directly formed on the surface of a substrate with no need of forming a resist having the periodic pattern that corresponds to the periodic structure; the microfluidic chip, and a surface plasmon resonance analyzing apparatus.